olaparib for Metastatic castration-resistant prostate cancer

Inclusion criteria

• {"criterion_text":"- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in the study protocol.\n- Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.\n- For inclusion in i) the optional exploratory genetic research and ii) the optional biomarker research, patients must fulfil the following criteria: - Provision of informed consent for genetic research prior to collection of sample. - Provision of informed consent for biomarker research prior to collection of sample. If a patient declines to participate in the optional exploratory genetic research or the optional biomarker research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study.\n- Patients must be ≥18 years of age (or ≥19 years of age in South Korea) at the time of signing the informed consent form. For patients enrolled in Japan who are <20 years of age, written informed consent should be obtained from the patient and from his legally acceptable representative.\n- Histologically or cytologically confirmed prostate adenocarcinoma.\n- Metastatic status defined as at least 1 documented metastatic lesion on either a bone scan or a CT/MRI scan.\n- First-line mCRPC.\n- Ongoing androgen deprivation with gonadotropin-releasing hormone analogue or bilateral orchiectomy, with serum testosterone <50 ng/dL (<2.0 nmol/L) within 28 days before randomisation. Patients receiving ADT at study entry should continue to do so throughout the study.\n- Candidate for abiraterone therapy with documented evidence of progressive disease.\n- Prior to randomisation, sites must confirm availability of either an archival FFPE tumour tissue sample, or a new biopsy taken during the screening window, which meets the minimum pathology and sample requirements in order to enable HRR status subgroup analysis of the primary endpoint rPFS. If there is not written confirmation of the availability of tumour tissue prior to randomisation, the patient is not eligible for the study.\n- Male patients must use a condom during treatment and for 3 months after the last dose of olaparib+abiraterone when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception (see Appendix I for acceptable methods) if they are of childbearing potential. Male patients should not donate sperm throughout the period of taking olaparib and for 3 months following the last dose of olaparib\n- Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment.\n- Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (see Appendix B), with no deterioration over the previous 2 weeks.\n- The participant has, in the opinion of the investigator, a life expectancy of at least 6 months."}

Exclusion criteria

• {"criterion_text":"- Has a known additional malignancy that has had progression or has required active treatment in the last 5 years.\n- Any previous exposure to a CYP17 (17α-hydroxylase/C17,20-lyase) inhibitor (eg, abiraterone, orteronel).\n- Patients with MDS/AML or with features suggestive of MDS/AML.\n- Clinically significant cardiovascular disease Association Class II-IV heart failure or cardiac ejection fraction measurement of <50% during screening as assessed by echocardiography or multigated acquisition scan.\n- Planned or scheduled cardiac surgery or percutaneous coronary intervention procedure.\n- Prior revascularisation procedure (significant coronary, carotid, or peripheral artery stenosis).\n- Uncontrolled hypertension (systolic BP ≥160 mmHg or diastolic BP ≥95 mmHg).\n- History of uncontrolled pituitary or adrenal dysfunction.\n- Active infection or other medical condition that would make prednisone/prednisolone use contraindicated.\n- Any chronic medical condition requiring a systemic dose of corticosteroid >10 mg prednisone/prednisolone per day.\n- Patients with known active hepatitis infection (ie, hepatitis B or C).\n- Any previous treatment with PARP inhibitor, including olaparib.\n- Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment. Patients who receive palliative radiotherapy need to stop radiotherapy 1 week before randomisation.\n- Patients who are unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.\n- Immunocompromised patients\n- Patients who are considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.\n- Persistent toxicities (Common Terminology Criteria for Adverse Events [CTCAEs] grade >2) caused by previous cancer therapy, excluding alopecia.\n- Patients with brain metastases. A scan to confirm the absence of brain metastases is not required.\n- Patients with spinal cord compression are excluded unless they are considered to have received definitive treatment for this and have evidence of clinically stable disease for 4 weeks.\n- Patients who are unevaluable for both bone and soft tissue progression\n- Patients who are unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.\n- Immunocompromised patients\n- Patients with known active hepatitis infection (ie, hepatitis B or C).\n- Any previous treatment with PARP inhibitor, including olaparib.\n- Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment. Patients who receive palliative radiotherapy need to stop radiotherapy 1 week before randomisation.\n- Patients with MDS/AML or with features suggestive of MDS/AML.\n- Any previous exposure to a CYP17 (17α-hydroxylase/C17,20-lyase) inhibitor (eg, abiraterone, orteronel).\n- Concomitant use of known strong CYP3A inhibitors (eg, itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg, ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks.\n- Concomitant use of known strong CYP3A inducers (eg, phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine or St John’s wort) or moderate CYP3A inducers (eg, bosentan, efavirenz or modafinil). The required period prior to starting study treatment is 5 weeks for phenobarbital and enzalutamide and 3 weeks for other agents.\n- Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.\n- Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).\n- Participation in another clinical study with an investigational product or investigational medical devices within 1 month of randomisation.\n- History of hypersensitivity to olaparib or abiraterone, any of the excipients of olaparib or abiraterone, or drugs with a similar chemical structure or class to olaparib or abiraterone.\n- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca and Merck staff and/or staff at the study site).\n- Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.\n- Previous randomisation in the present study."}

Primary endpoints

• {"endpoint_text":"- Radiological progression free survival (rPFS) defined as the time from randomisation to radiological progression, or death from any cause, whichever occurs first","definition_or_measurement_approach":"Time from randomisation to radiological progression assessed by the investigator according to RECIST 1.1 (soft tissue) and PCWG-3 criteria (bone), or death from any cause, whichever occurs first."}

Secondary endpoints

• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":"Overall survival (time from randomisation to death from any cause)."}
• {"endpoint_text":"- Time to first subsequent anticancer therapy or death (TFST)","definition_or_measurement_approach":"Time from randomisation to initiation of first subsequent anticancer therapy or death."}
• {"endpoint_text":"- Time to pain progression (TTPP)","definition_or_measurement_approach":"Time to documented progression of pain (as assessed by tools such as BPI-SF)."}
• {"endpoint_text":"- Time to first opiate use for cancer-related pain","definition_or_measurement_approach":"Time from randomisation to first use of opiates for cancer-related pain."}
• {"endpoint_text":"- Time to first symptomatic skeletal-related event (SSRE)","definition_or_measurement_approach":"Time from randomisation to first symptomatic skeletal-related event."}
• {"endpoint_text":"- Time to second progression or death (PFS2)","definition_or_measurement_approach":"Time from randomisation to second documented progression or death."}
• {"endpoint_text":"- BPI-SF: progression in pain severity domain, change in pain interference domain","definition_or_measurement_approach":"Assessment using Brief Pain Inventory - Short Form (BPI-SF) domains for pain severity and pain interference."}
• {"endpoint_text":"- FACT-P total score, FACT-G total score, trial outcome index, functional well-being, physical well being, prostate cancer subscale, and FACT Advanced Prostate Symptom Index 6 (FAPSI 6)","definition_or_measurement_approach":"Patient-reported outcomes assessed using FACT-P and FACT-G instruments and FAPSI-6 for prostate-specific symptoms and quality of life domains."}
• {"endpoint_text":"- HRR gene status","definition_or_measurement_approach":"Assessment of homologous recombination repair (HRR) gene mutation status (tumour and blood samples) including BRCA1, BRCA2, ATM and 11 other HRR genes."}
• {"endpoint_text":"- Plasma concentration data at steady state for olaparib, abiraterone, and Δ4-abiraterone in the subset of patients evaluable for PK","definition_or_measurement_approach":"Pharmacokinetic measurements of plasma concentrations at steady state for olaparib, abiraterone and Δ4-abiraterone in PK-evaluable subset."}

Belgium

Earliest CTIS Part Ii Submission Date

27-02-2024

Latest Decision Or Authorization Date

27-03-2024

Processing Time Days

29

Number Of Sites

1

Number Of Participants

20

France

Earliest CTIS Part Ii Submission Date

27-02-2024

Latest Decision Or Authorization Date

14-03-2024

Processing Time Days

16

Number Of Sites

1

Number Of Participants

60

Italy

Earliest CTIS Part Ii Submission Date

27-02-2024

Latest Decision Or Authorization Date

22-04-2024

Processing Time Days

55

Number Of Sites

2

Number Of Participants

25

Slovakia

Earliest CTIS Part Ii Submission Date

27-02-2024

Latest Decision Or Authorization Date

14-03-2024

Processing Time Days

16

Number Of Sites

2

Number Of Participants

20

Netherlands

Earliest CTIS Part Ii Submission Date

27-02-2024

Latest Decision Or Authorization Date

15-03-2024

Processing Time Days

17

Number Of Sites

1

Number Of Participants

25

Czechia

Earliest CTIS Part Ii Submission Date

27-02-2024

Latest Decision Or Authorization Date

15-03-2024

Processing Time Days

17

Number Of Sites

4

Number Of Participants

33

Primary sponsor

Full Name

AstraZeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden

Contract research organisations

Name

Fortrea Inc.

Responsibilities

sponsorDuties codes: 1,12,8,9; contact submissions@fortrea.com

Third parties

• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"sponsorDuties codes: 1,12,8,9; contact: submissions@fortrea.com","organisation_type":"Pharmaceutical company"}